NM_001276277.3:c.643-35G>A

Variant names:

• chr5-103147896-G-A
• rs77582921
• NM_001276277.3:c.643-35G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276277.3(PPIP5K2):​c.643-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,241,746 control chromosomes in the GnomAD database, including 917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (501 hom., cov: 32)
  • Exomes 𝑓: 0.016 (416 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 1 publications found

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive 100

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-103147896-G-A is Benign according to our data. Variant chr5-103147896-G-A is described in ClinVar as Benign. ClinVar VariationId is 1248014.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K2	NM_001276277.3	MANE Select	c.643-35G>A		intron	N/A	NP_001263206.1	O43314-1
	PPIP5K2	NM_001281471.3		c.643-35G>A		intron	N/A	NP_001268400.1	A0A087WZV0
	PPIP5K2	NM_001345873.2		c.643-35G>A		intron	N/A	NP_001332802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K2	ENST00000358359.8	TSL:1 MANE Select	c.643-35G>A		intron	N/A	ENSP00000351126.3	O43314-1
	PPIP5K2	ENST00000414217.5	TSL:1	c.643-35G>A		intron	N/A	ENSP00000416016.1	O43314-2
	PPIP5K2	ENST00000613674.4	TSL:2	c.643-35G>A		intron	N/A	ENSP00000482907.1	A0A087WZV0

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7766 AN: 151872 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0383

GnomAD2 exomes AF: 0.0204 AC: 4290 AN: 210214 AF XY: 0.0171

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00873

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00283

Gnomad NFE exome AF: 0.0134

Gnomad OTH exome AF: 0.0169

GnomAD4 exome AF: 0.0158 AC: 17247 AN: 1089756 Hom.: 416 Cov.: 14 AF XY: 0.0148 AC XY: 8190 AN XY: 554036

African (AFR) AF: 0.160 AC: 3881 AN: 24250

American (AMR) AF: 0.0111 AC: 348 AN: 31372

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 153 AN: 21212

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37216

South Asian (SAS) AF: 0.00124 AC: 87 AN: 70292

European-Finnish (FIN) AF: 0.00344 AC: 178 AN: 51734

Middle Eastern (MID) AF: 0.0124 AC: 60 AN: 4850

European-Non Finnish (NFE) AF: 0.0145 AC: 11657 AN: 801554

Other (OTH) AF: 0.0187 AC: 882 AN: 47276

GnomAD4 genome AF: 0.0512 AC: 7787 AN: 151990 Hom.: 501 Cov.: 32 AF XY: 0.0487 AC XY: 3620 AN XY: 74296

African (AFR) AF: 0.157 AC: 6523 AN: 41480

American (AMR) AF: 0.0157 AC: 239 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 901 AN: 67846

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0147 Hom.: 22

Bravo AF: 0.0574

Asia WGS AF: 0.00868 AC: 30 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.26
DANN	Benign	0.36
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77582921; hg19: chr5-102483600;